1.Novel hybrids of (phenylsulfonyl)furoxan and N-benzyl matrinol as anti-hepatocellular carcinoma agents.
Li-qin HE ; Qi YANG ; Ya-xian WU ; Xiao-shan WANG
Acta Pharmaceutica Sinica 2015;50(5):574-578
N-Benzyl matrinol was obtained by hydrolysis, benzylation and reduction reaction from matrine. A series of hybrids (8a-8n) from (phenylsulfonyl)furoxan and N-benzyl matrinol were synthesized and biologically evaluated as anti-hepatocellular carcinoma agents. All target compounds were evaluated for anti-proliferative activity against human hepatocellular Bel-7402, SMMC-7721, Bel-7404, and HepG2 cells in vitro by MTT method. The results indicated that all of these compounds had potent anti-proliferative activity which were more potent than their parent compound and 5-FU, especially 8a-8h and 8j showed the strongest anti-HCC HepG2 cell activity with IC50 values of 0.12-0.93 μmol x L(-1).
Antineoplastic Agents
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pharmacology
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Carcinoma, Hepatocellular
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Fluorouracil
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Hep G2 Cells
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Humans
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Liver Neoplasms
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Oxadiazoles
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pharmacology
2.The relationship between four GWAS-identified single nucleotide polymorphisms and female breast canc-er in Henan population
Yaning HE ; Qi CHEN ; Hui LIU ; Xianfu SUN ; Chaojun LIU ; Yingbo SHAO ; Ya ZHAO
Chinese Journal of Endocrine Surgery 2015;(5):367-371
Objective To verify the association between common breast cancer susceptibility loci which have been confirmed in European and Asian populations and breast cancer susceptibility in sporadic breast cancer among the Han nationality in Henan province , and to analyze their genotypes in the internal type of breast cancer . Methods In 253 breast cancer patients ( the case group ) and 343 patients who had benign breast lesions ( the control group), rs2046210(6q25.1), rs2981582(EGFR2), rs889312(MAP3K1), and rs3803662(TOX3/TNRC9)were genotyped by SNP im-LDR technique.According to estrogen receptor(ER), progesterone receptor (PR), human epidermal growth factor receptor 2(HER2)and Ki67, breast cancer are divided into 5 types:Lu-minal A, Luminal B, HER2-enrich, Luminal HER2, and triple negative breast cancer ( TNBC).Results rs2046210(6q25.1), rs2981582(EGFR2), rs889312(MAP3K1)had no statistical differences between the case group and the control group(P=0.421, 0.459, and 0.468), but the genotype of rs3803662(TOX3/TNRC9)in the case group and the control group had statistical difference (P=0.037).The allelic frequencies of rs3803662 between the case group and control group were different in codominant inheritance ( OR=2.19, 95%CI:1.19-4.02)and recessive genetic models (OR =2.06,95% CI:1.15 -3.70).Compared with AA and GA, GG in-creased the risk of breast cancer ( P =0.012, 0.015 ).The genotypes of rs2046210 ( 6q25.1 ), rs2981582 (EGFR2), rs889312(MAP3K1), and rs3803662(TOX3/TNRC9)had no difference in different types of breast cancer.Conclusions Four common breast cancer susceptibility loci from GWAS are not entirely associated with breast cancer risk among the Han nationality in Henan province .Only rs3803662(TOX3/TNRC9)is confirmed to increase the risk of breast cancer .Different genotypes of 4 loci distribute equally in different types of breast cancer .
3.Clinical effect of anterior vitrectomy for congenital cataract
Hua, HE ; Feng, ZHOU ; Qi, ZHU ; Qian, WANG ; Xue-Mei, WU ; Jian, MA ; Ya-Yun, WANG
International Eye Science 2015;(5):825-827
?AlM: To evaluate the clinical efficacy of posterior continuous curvilinear capsulorhexis ( PCCC ) combined with anterior vitrectomy in preventing posterior capsule opacification of congenital cataract surgery.
?METHODS:Postoperative clinical follow-up data of 82 cases ( 87 eyes ) with congenital cataract treated in Eye Center of our hospital from January 2011 to August 2014 were retrospectively analyzed. The patients were divided into the surgical control group ( 38 cases, 40 eyes, recieved phacoemulsification + PCCC ) and the study group ( 44 cases, 47 eyes, accepted phacoemulsification+ PCCC + anterior vitrectomy). The incidence of central optic axis opaque and postoperative visual acuity distribution were recorded at 1a follow - up. lntraoperative and postoperative complications were observed.
?RESULTS:The rate of central optic axis opaque grade 0 in control group was 37. 5%, compared to 76. 6% in study groups. The opacity distribution ratio of grade 1,2,3 and 4 in study group were lower than that of control group, and the central optic axis opacity distribution ratio in study group was significantly better than that of control group (P<0. 05). The 19 eyes(47. 5%) of visual acuity testing ≤0. 5 in control group , was higher than the 7 eyes(14. 89%) of that in the study group, The 21 eyes (52. 5%) of visual acuity testing >0. 5 in control group was lower than the 40 eyes ( 85. 11%) of that in study group. The visual acuity between two groups has statistical significance difference after 1a follow-up ( P<0. 05 ) , and the visual acuity in study group was significantly better than that in the control group. The postoperative intraocular pressure at 1mo and 1a follow-up was lower than before operation in two groups ( P<0. 05), but there was no significant difference between two groups in intraocular pressure (P<0. 05).
?CONCLUSlON: Combination of phacoemulsification, PCCC and anterior vitrectomy presents reliable clinical effects on postoperative central optic axis opacity distribution ratio and visual acuity, and it should be adopted to prevent the occurrence of posterior capsule opacification.
4.Research progress of ionizable lipid nanoparticles for siRNA delivery
Ya-nan ZHAO ; Wei HE ; Quan-lin SHAO ; Hua-yu LIU ; Ming-qi LIU ; Ran MO
Acta Pharmaceutica Sinica 2023;58(8):2292-2299
Small interfering RNA (siRNA) is the initiator of RNA interference and inhibits gene expression by targeted degradation of specific messenger RNA. siRNA-mediated gene regulation has high efficiency and specificity and exhibits great significance in the treatment of diseases. However, the naked or unmodified siRNA has poor stability, easy to degrade by nuclease, short half-life, and low intracellular delivery. As an emerging non-viral nucleic acid delivery system, ionizable lipid nanoparticles play an important role in improving the druggability of siRNA. At present, one siRNA drug based on ionizable lipid nanoparticles has been approved for the treatment of rare disease. This review introduces the research progress in ionizable lipid nanoparticles for siRNA delivery, focusing on the effect of each component of lipid nanoparticles on the efficiency of siRNA-mediated gene silencing, which provides new references for the studies on ionizable lipid nanocarriers for siRNA delivery.
5.Neurobehavioral function of neonatal mice following excitotoxic brain damage.
Zhi-Ye QI ; Xiang-Ying HE ; Qi LI ; Ya-Xiong MO ; Kun LIANG
Chinese Journal of Contemporary Pediatrics 2009;11(3):191-193
OBJECTIVETo assess the changes of neurobehavioral function in a neonatal mouse model of excitotoxic brain damage.
METHODSFifty-five 5-day-old ICR neonatal mice were randomly assigned to three groups: blank (no intravenous) control (n=20), saline control (n=20) and excitotoxic brain damage model (ibotenic acid treatment, n=15). Behavioral function was evaluated by the surface righting reflex test (postnatal days 6-10), the swimming test (postnatal days 8-12) and the Y-maze discrimination learning test (postnatal days 33-34).
RESULTSRighting time in the surface righting reflex test in the ibotenic acid treatment group on postnatal days 6-10 was more prolonged than that in the two control groups (p<0.05). Swimming test scores in the ibotenic acid treatment group were significantly lower than those in the two control groups (p<0.05). In the Y-maze discrimination learning test, the mice from the ibotenic acid treatment group performed significantly worse than two control groups, presenting with increased learning times (19.79+/-2.42 vs 16.29+/-2.48 or 16.30+/-2.37; p<0.05) and achieving a lower correct percentage (86.7% vs 96.5% or 95.0%) (p<0.05).
CONCLUSIONSThe developmental reflexes and learning and memory functions were impaired in neonatal mice following excitotoxic brain damage. Behavioral testing is useful in the evaluation of early developmental reflexes and long-term neurobehavioral outcome in neonatal mice with excitotoxic brain damage.
Animals ; Animals, Newborn ; Behavior, Animal ; drug effects ; Brain ; drug effects ; Excitatory Amino Acid Agonists ; toxicity ; Female ; Ibotenic Acid ; toxicity ; Male ; Maze Learning ; drug effects ; Mice ; Mice, Inbred ICR ; Swimming
6.Mechanism of PC12 cell differentiation induced by total salvianolic acid
Yang SHEN ; Qi ZHANG ; Jia-Qi ZHAO ; Ya-Juan TIAN ; Qin-Qing LI ; Shi-Feng CHU ; Wen-Bin HE
Chinese Journal of Pharmacology and Toxicology 2018;32(2):99-104
OBJECTIVE To study the differentiation of PC12 cells induced by total salvianolic acid (Tsa) and the mechanism. METHODS MTT assay was used to detect the effect of Tsa 0.01, 0.1 and 1.0 μg·L-1on proliferation of PC12 cells and on the cells damaged by oxygen and glucose deprivation (OGD).The number of projections of PC12 cells was statistically analyzed.Western blotting was applied to detect the levels of microtubule-associated protein2 (MAP-2), extracellular signal-regulated kinase1/2 (ERK1/2), phosphorylated ERK1/2(p-ERK1/2), mitogen-activated protein kinase kinase1/2(MEK1/2) and p-MEK1/2 proteins.MEK inhibitor U0126 was examined for its effect on expressions of p-ERK1/2 and ERK1/2 protein in PC12 cells induced by Tsa 1.0 μg·L-1.RESULTS Compared with normal control group, Tsa 1.0 μg·L-1could promote PC12 cell proliferation, and the survival rate was increased by 90%, but the survival rate of PC12 cells was not affected by Tsa 0.01 or 0.1 μg·L-1. Compared with OGD injured group,PC12 cells injured by OGD could be repaired by Tsa 0.1 or 1.0 μg·L-1,and the survival rate was increased to (47.7±1.8)% and (63.2±13.0)%, respectively (P<0.05, P<0.01). Compared with normal control group,Tsa 0.01,0.1 and 1.0 μg·L-1could promote the growth of PC12 cell projections (P<0.01). Western blotting results showed that Tsa could promote the expressions of MAP-2, p-ERK1/2 and p-MEK1/2 proteins, and this effect could be blocked by U0126 inhibitor (P<0.01). CONCLUSION Tsa can induce the proliferation and differentiation of PC12 cells, the mechanism of which is possibly the activation of p-MEK and p-ERK1/2.
7.Hipbone biomechanical finite element analysis and clinical study after the resection of ischiopubic tumors.
He YA-QI ; Zhang XUE-LIN ; Tang BING-HANG ; Yang ANG
Chinese Medical Sciences Journal 2012;27(3):153-160
OBJECTIVETo investigate the changes of hipbone biomechanics after the resection of ischiopubic tumors and their relationships with the complications in the convalescent stage, and directing the postoperative pelvic reconstruction.
METHODSDICOM data were used to create an intact hipbone finite element model and postoperative model. The biomechanical indices on the same region in the two models under the same boundary condition were compared. The differences of displacement, stress, and strain of the two models were analyzed with statistical methods.
RESULTSThe distribution areas of the hipbone nodes' displacement, stress, and strain were similar before and after the simulated operation. The sacroiliac joint nodes' displacement (P=0.040) and strain (P=0.000), and the acetabular roof nodes' stress (P=0.000) and strain (P=0.005) of two models had significant differences, respectively.But the sacroiliac joint nodes' stress (P=0.076) and the greater sciatic notch nodes' stress (P=0.825) and strain (P=0.506) did not have significant differences.
CONCLUSIONSThe resection of ischiopubic tumors mainly affect the biomechanical states of the homolateral sacroiliac joint and acetabular roof. The complications in the convalescent stage are due to the biomechanical changes of the sacroiliac joint and the acetabular roof and disappearances of the stabilization and connection functions of the pubic symphysis and superior ramus of pubis.
Acetabulum ; physiopathology ; Biomechanical Phenomena ; Finite Element Analysis ; Humans ; Pelvic Bones ; physiopathology ; Pelvic Neoplasms ; physiopathology ; surgery ; Sacroiliac Joint ; physiopathology
8.The construction of a novel recombinant virus Δ67R-RGV and preliminary analyses the function of the 67R gene.
Xing HUANG ; Chao PEI ; Li-Bo HE ; Qi-Ya ZHANG
Chinese Journal of Virology 2014;30(5):495-501
The Rana grylio virus (RGV) is a member of the genus Ranavirus. It belongs to the family Iridoviridae, and contains the gene 67R encoding dUTPase. In order to investigate the function of 67R in the replication and infection of RGV, we constructed Δ67R-RGV, a recombinant virus with deletion of 67R. First, we constructed the plasmid pGL3-67RL-p50-EGFP-67RR which carried an enhanced green fluorescence gene (EGFP) as a selectable marker. After homologous recombination between pGL3-67RL-p50-EG- FP-67RR and the RGV genome, Epithelioma papulosum cyprini (EPC) cells were infected with the resulting mixture. Through ten successive rounds of plaque isolation via EGFP selection, all plaques emitted green fluorescence, and finally Δ67R-RGV was generated. Total DNA of Δ67R-RGV infected cells was extracted for PCR analyses. Simulateously, mock infected and wild-type RGV (wt-RGV) infected cells were used as a comparison. Results showed that 67R could be detected in wt-RGV infected cells, but that only the EGFP gene was detected in Δ67R-RGV infected cells. Furthermore, one-step growth curves of wt-RGV and Δ67R-RGV were similar. Therefore, 67R and its encoding product dUTPase might not be essential for the growth of RGV. These results suggest that, homologous recombination and recombinant rana- virus could be used to study the gene function of viruses in aquatic animals.
Genes, Viral
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physiology
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Genome, Viral
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Polymerase Chain Reaction
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Pyrophosphatases
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genetics
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Ranavirus
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genetics
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Recombination, Genetic
9.Nucleotides sequence analysis of EV71 Chinese strain SHZH98 3C segment.
Ya-qing HE ; Fan YANG ; Liang-cheng LI ; Qi JIN
Chinese Journal of Experimental and Clinical Virology 2003;17(4):354-357
OBJECTIVETo study the EV71 Chinese strain SHZH98 and analyze its genetic evolution using 3c gene as index.
METHODSThe 3C gene cDNA of EV71 Chinese strain SHZH98 was amplified by PCR, the PCR product was sequenced.
RESULTSThe EV71 Chinese mainland strain SHZH98 3C segment was 549 bps in length. Comparison of nucleotide sequences from other enteroviruses which have been published, revealed a higher homology to strain MS, 78.7% at nucleotide level and 93.45% at deduced amino acid level. The homology to strain BrCr was 76.7% at nucleotide level and 89.1% at deduced amino acid level. Taiwan strains POLY,NCKU,TW2086,TW2272 shared a lower homology with Chinese mainland strain SHZH98, 74.0%, 73.8%, 71.9%, 69.8% at nucleotide level and 90.7%, 90.2%, 84.2%, 82.5% at deduced amino acid level. The genetic progress analysis revealed that EV71 Chinese mainland strain SHZH98 3C segment shares more homology with European and American strains than Taiwan strains.
CONCLUSIONThe non-structural protein of EV71 Chinese strains may have different evolutionary process from Taiwan strains.
Amino Acid Sequence ; Base Sequence ; Enterovirus ; genetics ; isolation & purification ; Genes, Viral ; Humans ; Molecular Sequence Data ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid
10.Treating primary liver cancer patients by Pi-strengthening and Qi-regulating method: univariate and multivariate analyses of their prognoses.
Xiao-Bing YANG ; Shun-Qin LONG ; Wan-Yin WU ; Hong DENG ; Zong-Qi PAN ; Wen-Feng HE ; Yu-Shu ZHOU ; Gui-Ya LIAO
Chinese Journal of Integrated Traditional and Western Medicine 2014;34(2):162-166
OBJECTIVETo evaluate the prognostic factors in treating primary liver cancer (PLC) patients by Pi-strengthening and qi-regulating method (PSQRM), thus providing evidence and optimizing Pi-strengthening and qi-regulating program.
METHODSClinical data of 151 PLC patients treated by PSQRM at Oncology Department, Guangdong Provincial Hospital of Traditional Chinese Medicine from May 2007 to March 2009 were retrospectively analyzed. The univariate analysis was determined to analyze possible prognostic factors. Selected key factors were introduced into the COX proportional hazard model, and multivariate analysis was carried out.
RESULTSThe 1-year survival rate was 21.85%, the median survival time was 6.80 months, and the mean survival time was 8.98 months. The univariate analysis showed that Chinese medicine (CM) syndrome types, clinical symptoms at the initial diagnosis, ascites, tumor types, ratios of foci, portal vein tumor thrombus, intrahepatic metastasis, a-fetoprotein (AFP) levels, total bilirubin classification, albumin classification, Child-Pugh classification, and domestic staging of liver cancer were significant prognostic factors (P < 0.05). The statistic data of multivariate analysis indicated that CM syndrome types, ascites, tumor types, portal vein tumor thrombus, AFP levels, Child-Pugh classification, and domestic staging of liver cancer were independent factors influencing prognosis (P < 0.05).
CONCLUSIONThe prognosis of PLC treated with PSQRM is determined by multiple factors including CM syndrome types, ascites, tumor types, portal vein tumor thrombus, AFP levels, Child-Pugh classification, and domestic staging of liver cancer.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; epidemiology ; therapy ; Female ; Humans ; Liver Neoplasms ; epidemiology ; therapy ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Survival Rate ; Treatment Outcome